Prostate cancer is the second leading cause of cancer-related deaths among American men with an estimated incidence of 218,890 cases and an estimated number of 27,050 deaths in 2007. The majority of prostate cancer is diagnosed at a localized stage, and is treated with prostatectomy or radiation therapy. However, some patients are diagnosed with metastatic disease or recurrent disease after treatment of localized disease. Androgen ablation is the standard treatment for metastatic or recurrent disease. However, some patients eventually develop androgen-independent prostate cancer (metastatic, hormone-refractory prostate cancer [mHRPC]). At this stage of metastatic disease, the chemotherapeutic agent docetaxel has been demonstrated to confer a survival benefit of 1.9 to 2.4 months in randomized clinical trials.

Docetaxel therapy may fail due to progressive disease or toxicity. On June 17, 2010, the FDA approved cabazitaxel (Jevtana Injection, sanofi-aventis) for use in combination with prednisone for treatment of patients with mHRPC previously treated with a docetaxel-containing regimen. Cabazitaxel—which, like docetaxel, is part of a class of drugs known as taxanes—was designed to be active in cells that develop resistance to docetaxel. Cabazitaxel is a microtubule inhibitor. Cabazitaxel binds to tubulin and promotes its assembly into microtubules while simultaneously inhibiting disassembly. This leads to the stabilization of microtubules, which results in the inhibition of mitotic and interphase cellular functions. The drug appears to elude a mechanism in prostate cancer cells that pumps anticancer drugs out of the cells before they have a chance to be effective.

Policy

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Medically Necessary

BCBSMT may consider Cabazitaxel (Jevtana®) in combination with prednisone medically necessary when the following criteria are met:

Progressive measurable disease, as evidenced by changes in size of lymph nodes or parenchymal masses on physical examination or radiographic studies; or

Bone scan progression, as evidenced by one or more new lesions or increase in size of lesions (not including "flare" that occurs at commencement of hormonal therapy or chemotherapy); or

PSA progression: An increase in PSA over a previous reference value, where the PSA value is a measurement at a minimum of one week from the reference value, and the PSA measurement is a minimum of 25 percent greater than the reference value, and an absolute-value increase in PSA of at least 5 ng/ml over the reference value, and this PSA increase is confirmed by a second value.

Investigational

All other uses of cabazitaxel (Jevtana®) is considered experimental, investigational and unproven.

NOTE: BLACK BOX WARNING

The following information was taken directly from the Food and Drug Administration (FDA) Jevtana product labeling:

Neutropenic deaths have been reported. Obtain frequent blood counts to monitor for neutropenia. Do not give Jevtana if neutrophil counts of ≤1,500 cells/mm3.

Severe hypersensitivity can occur and may include generalized rash/erythema, hypotension, and bronchospasm. Discontinue Jevtana immediately if severe reactions occur and administer appropriate therapy.

Contraindicated if history of severe hypersensitivity reactions to Jevtana® or to drugs formulated with polysorbate 80.

Rationale

The FDA approval of Jevtana is based primarily on the results of a randomized, open-label, international trial of 755 patients from 146 sites in 26 countries in Europe, USA, South America, and Asia Pacific regions. The study spanned January 2, 2007 to September 25, 2009. This study included patients over 18 years of age (range 49-62) with hormone-refractory metastatic prostate cancer either measurable by RECIST (Response Evaluation Criteria In Solid Tumors) criteria or non-measurable disease with rising PSA levels or appearance of new lesions, and ECOG (Eastern Cooperative Oncology Group) performance status 0-2. Patients had to have neutrophils >1,500 cells/mm3, platelets > 100,000 cells/mm3, hemoglobin > 10 g/dL, creatinine < 1.5 x upper limit of normal (ULN), total bilirubin < 1 x ULN, AST < 1.5 x ULN, and ALT < 1.5 x ULN. Patients with a history of congestive heart failure, or myocardial infarction within the last six months, or patients with uncontrolled cardiac arrhythmias, angina pectoris, and/or hypertension were not included in the study. Patients were randomized to receive either cabazitaxel 25 mg/m2 intravenously every three weeks in combination with prednisone 10 mg/day, or mitoxantrone 12 mg/m2 intravenously every three weeks in combination with prednisone 10 mg/day. Patients were treated until disease progression, death, unacceptable toxicity, or completion of 10 cycles of therapy.

Deaths due to causes other than disease progression within 30 days of the last dose were reported in 18 (5%) cabazitaxel-treated patients and three (<1%) mitoxantrone-treated patients. The most common fatal adverse reactions in cabazitaxel-treated patients were infections (n=5), and renal failure (n=4). One death was due to diarrhea-induced dehydration and electrolyte imbalance.

Because of the risk of severe hypersensitivity, patients should be premedicated with an antihistamine, a corticosteroid and an H2 antagonist. In addition, antiemetic prophylaxis is recommended.

The National Comprehensive Cancer Network (NCCN) panel recommendations include cabazitaxel as an option for second-line therapy after docetaxel failure for men with mHRPC. The NCCN advises physicians to follow current guidelines for prophylactic white blood cell growth factor use; to provide supportive care, including antiemetics and symptom-directed anti-diarrheal agents; and to stop cabazitaxel upon clinical disease progression or intolerance. In addition, cabazitaxel has not been tested in patients with hepatic dysfunction and should not be used on these patients.

Coding

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

®Registered marks of the Blue Cross and Blue Shield Association, an association of independent Blue Cross and Blue Shield Plans. ®LIVE SMART. LIVE HEALTHY. is a registered mark of BCBSMT, an independent licensee of the Blue Cross and Blue Shield Association, serving the residents and businesses of Montana.